Loosening, the major cause of prosthetic hip failure is caused by peri-prosthetic osteolysis. The pathophysiology of peri-prosthetic osteolysis has been an area of intense investigation at the University of Rochester, and great progress has been made in understanding the basic mechanisms of this process. Based on our understanding of these mechanisms, a number of potential therapies for peri-prosthetic osteolysis have been proposed and some have been successful in an animal model. Now clinical trials are needed to translate this basic research into clinically useful therapies. A major hurdle to such trial is the relative imprecision of the methods that have been used to of measure peri-prosthetic osteolysis. Recent developments in CT image analysis now allow measurement of osteolysis with great precision. These advances in image analysis now promise to make clinical trials technically feasible. However, the design of trials depends not only on the precision with which loosening can be measured but also on the natural history of loosening itself. Therefore, the primary focus of this proposal will be the natural history of acetabular osteolysis investigated using different imaging modalities including newly developed CT scan software that allows artifact suppression, virtual reconstruction, and volumetric measurements of osteolytic lesions. Information on natural history of acetabular osteolysis with different imaging modalities will allow determination of sample size, duration of therapy, and the best strategies for the selection, screening, and following different subsets of study subjects. A secondary focus of this proposal will be the evaluation of the role of host factors in determining the rate of pen-prosthetic Osteolysis. Aim #1. Natural History. Acetabular osteolysis will be investigated in a cross-sectional study using CT imaging in three groups of subjects selected to represent the spectrum of osteolysis. Aim #2. Imaging. Sensitivity and specificity of plain films and conventional CT scan for the presence of acetabular osteolysis and for progression of osteolysis will be determined using CT scans with artifact suppression and virtual reconstruction of osteolytic lesions (3D- segmented CT) as the gold standard. Aim #3. Host Factors. The role of host factors in acetabular bone loss will be determined by studying patients with bilateral total hip arthroplasties and comparing intra- and inter-individual variance in wear rates and osteolysis. In addition, DNA and serum samples from all subjects studied in this proposal will be banked.